Abstract
Excessive fructose intake has been associated with the development and progression of pancreatic cancer. This study aimed to elucidate the relationship between fructose utilization and pancreatic cancer progression. Our findings revealed that pancreatic cancer cells have a high capacity to utilize fructose and are capable of converting glucose to fructose via the AKR1B1-mediated polyol pathway, in addition to uptake via the fructose transporter GLUT5. Fructose metabolism exacerbates pancreatic cancer proliferation by enhancing glycolysis and accelerating the production of key metabolites that regulate angiogenesis. However, pharmacological blockade of fructose metabolism has been shown to slow pancreatic cancer progression and synergistically enhance anti-tumor capabilities when combined with anti-angiogenic agents. Overall, targeting fructose metabolism may prove to be a promising therapeutic approach in the treatment of pancreatic cancer.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening (2023B1212120005).
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W.J. conceptualized the study. W.J and C.W. designed the study and coordinated the experimental planning. C.W. and L.W. performed the experiments. C.W., J.M., X.Y, and Y.L. were responsible for mouse experiments. C.W. was responsible for cell studies. C.W. and L.W. were responsible for sample preparation and metabolomics analysis. C.W. K.C. and L.W. performed the data preprocessing and statistical analysis. C.W. and W.J. drafted the manuscript and produced the figures. G.M., A.L., H.B., Q.Z., J.K. and K.C. provided valuable suggestions in data analysis and interpretation. W.J. and C.W. critically revised the manuscript.
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All animal experiments were approved by the Research Ethics Committee of the Hong Kong Baptist University (REC/20–21/0584) and were performed in accordance with relevant guidelines and regulations. The relevant licenses were also approved by the Department of Health, Hong Kong, China (22-145 in DH/HT&A/8/2/6 Pt.6. and 21-189 in DH/HT&A/8/2/6 Pt.4.).
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Wang, C., Wang, L., Zhao, Q. et al. Exploring fructose metabolism as a potential therapeutic approach for pancreatic cancer. Cell Death Differ 31, 1625–1635 (2024). https://doi.org/10.1038/s41418-024-01394-3
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DOI: https://doi.org/10.1038/s41418-024-01394-3
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